Nathan 2006

Methods	A parallel‐group, multi‐centre study over 12 weeks
Participants	365 adults and adolescents randomised Age range: 12 to 82 years; mean FEV₁ 68% predicted Inclusion criteria: fluticasone propionate 440 to 660 μg/d for ≥ 3 months before study entry; FEV₁ 40% to 85%; reversibility ≥ 15%
Interventions	Fluticasone propionate and salmeterol HFA 110/42 twice daily (220/84) vs CFC salmeterol 42 twice daily (84) vs CFC fluticasone 110 twice daily (220) vs HFA placebo Inhaler devices: MDI Run‐in: 2 weeks This review includes only data from the fluticasone propionate and salmeterol and fluticasone arms Co‐interventions: ICS at usual dose was an inclusion criterion, but it appears to have been withdrawn in the salmeterol and placebo arms of the study
Outcomes	The paper publication mentions 1 drug‐related SAE (an upper gastrointestinal bleed from the placebo group) Website: SAS30004 No fatal SAE. No SAE on fluticasone propionate/salmeterol or fluticasone propionate
Notes	Sponsored by GSK
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not stated
Allocation concealment (selection bias)	Unclear risk	Not stated
Blinding (performance bias and detection bias) All outcomes	Low risk	Double‐blind
Independent Assessment of causation (detection bias) Asthma‐related events	High risk	Causation of SAEs not independently assessed
Incomplete outcome data (attrition bias) All outcomes	Low risk	243/365 (67%) completed the study; no SAEs occurred
Selective reporting (reporting bias)	Low risk	Full data on GSK website